Analysis of the copy number profiles of several tumor samples from the same patient reveals the successive steps in tumorigenesis

We present a computational method, TuMult, for reconstructing the sequence of copy number changes driving carcinogenesis, based on the analysis of several tumor samples from the same patient. We demonstrate the reliability of the method with simulated data, and describe applications to three different cancers, showing that TuMult is a valuable tool for the establishment of clonal relationships between tumor samples and the identification of chromosome aberrations occurring at crucial steps in cancer progression.     

Chaotic gene regulatory networks can be robust against mutations and noise

Robustness to mutations and noise has been shown to evolve through stabilizing selection for optimal phenotypes in model gene regulatory networks. The ability to evolve robust mutants is known to depend on the network architecture. How do the dynamical properties and state-space structures of networks with high and low robustness differ? Does selection operate on the global dynamical behavior of the networks? What kind of state-space structures are favored by selection? We provide damage propagation analysis and an extensive statistical analysis of state spaces of these model networks to show that the change in their dynamical properties due to stabilizing selection for optimal phenotypes is minor. Most notably, the networks that are most robust to both mutations and noise are highly chaotic. Certain properties of chaotic networks, such as being able to produce large attractor basins, can be useful for maintaining a stable gene-expression pattern. Our findings indicate that conventional measures of stability, such as damage propagation, do not provide much information about robustness to mutations or noise in model gene regulatory networks.     

Permeability of three boreal forest landscape types to bird movements as determined from experimental translocations

Efficient dispersal is critical to metapopulation persistence in fragmented landscapes. Yet, this phenomenon is poorly understood because it is difficult to study. We used an indirect method, experimental translocation, to investigate the permeability of three landscape types of the boreal mixedwood forest region of Canada to movements of a forest specialist, the ovenbird (Seiurus aurocapillus), and a habitat generalist, the white-throated sparrow (Zonotrichia albicollis). We captured a total of 148 males (84 ovenbirds; 64 sparrows), which were then colour banded and displaced ca. 2 km away from their territories in landscapes fragmented either by agriculture, timber harvesting, or natural disturbances. We measured the probability and time of return of individuals to their territories during the 48 h following their translocation. We examined the relative influence of landscape type, territory quality, and age, physical characteristics, and pairing status of individuals on their probability or time of return. For both species, landscape type was the only significant predictor of the probability and time of return of individuals. For the ovenbird, the agricultural landscape was least permeable, followed by the harvested and naturally patchy landscapes. The agricultural and harvested landscapes were equally permeable to white-throated sparrow movements, and the naturally patchy landscape was the least permeable. Permeability to ovenbird movements increased with the proportion of forest in the landscape. Because matrix type and the proportion and configuration of forest differed significantly among the three landscape types, we could not determine their relative influence on landscape permeability to bird movements. However, our results do indicate that even a long-distance migrant such as the ovenbird can move more rapidly and efficiently across the landscape as the proportion of suitable (or permeable) habitat increases.     

Purification and identification of sperm surface proteins and changes during epididymal maturation

Surface membrane proteins have a key role in the sequential interactions between spermatozoa and oocytes. The aim of this study was to characterize protein changes occurring during post-testicular differentiation using a new overall approach to study surface membrane proteins of spermatozoa. A dedicated protocol based on specific purification of surface membrane proteins labeled with sulfo-NHS-SS-biotin was developed for this purpose. Appropriate gel electrophoresis separation and purification methods combined with standard proteomic methods were then used to identify and quantify surface membrane proteins from immature and mature spermatozoa. Membrane-associated proteins were discriminated from integral membrane proteins by differential solubilization. Protein regionalization on the spermatozoon surface was achieved by comparative analysis of the surface protein extracts from the entire spermatozoa and from periacrosomal sperm plasma membranes. Identification of several known proteins and of new proteins related to the process of epididymal maturation showed the reliability of this protocol for specific purification of a subproteome and identification of new sperm membrane proteins. This approach opens up a new area in the search for male fertility markers.     

Generalized estimating equations approach for spatial lattice data: A case study in adoption of improved maize varieties in Mozambique

Generalized estimating equations (GEE) are extension of generalized linear models (GLM) widely applied in longitudinal data analysis. GEE are also applied in spatial data analysis using geostatistics methods. In this paper, we advocate application of GEE for spatial lattice data by modeling the spatial working correlation matrix using the Moran's index and the spatial weight matrix. We present theoretical developments and results for simulated and actual data as well. For the former case, 1,000 samples of a random variable (response variable) defined in (0, 1) interval were generated using different values of the Moran's index. In addition, 1,000 samples of a binary and a continuous variable were also randomly generated as covariates. In each sample, three structures of spatial working correlation matrices were used while modeling: The independent, autoregressive, and the Toeplitz structure. Two measures were used to evaluate the performance of each of the spatial working correlation structures: the asymptotic relative efficiency and the working correlation selection criterions. The results showed that both measures indicated that the autoregressive spatial working correlation matrix proposed in this paper presents the best performance in general. For the actual data case, the proportion of small farmers who used improved maize varieties was considered as the response variable and a set of nine variables were used as covariates. Two structures of spatial working correlation matrices were used and the results showed consistence with those obtained in the simulation study.     

Tactile perception and manual dexterity in computer users

Recent studies suggest that sensory input generated during highly repetitive tasks can degrade the sensory representation of the hand and eventually lead to sensory and motor problems. In this study, we investigated whether early changes in tactile perception and manual dexterity could be detected in persons exposed to computer tasks. Performance in tests designed to assess tactile perception (grating orientation task for spatial acuity and roughness discrimination) and manual dexterity (grooved pegboard test) was compared between two groups of healthy individuals, matched for age, gender, and experience, who differed in terms of computer habits. One group consisted of frequent users (FU, > 2 h/day, n = 36) and the other of non or occasional users (OU, < 2 h/day, n = 28). Comparison of performance between groups with subjects sorted by gender revealed significant differences ( t -test, p < 0.05) in female, but not male, participants. Grating resolution thresholds at the tip on the second and fifth digits were, on average, 40% higher in female FU ( n = 13) than in female OU ( n = 10) and performance scores on the dexterity test were significantly higher for the left hand. The results of this study indicate that early signs of deterioration in hand function can be present in persons constantly exposed to computer tasks and that these signs are more readily apparent in women than in men. The loss of tactile spatial acuity found in female FU possibly reflect an early consequence of the degraded sensory representation of the hand resulting from constant repetitions of fine motor tasks.     

Syntheses and properties of trimethylaminophenoxy-substituted Zn((II))-phthalocyanines

The syntheses, photophysical properties and in vitro biological behavior of a series of nine Zn((II))-phthalocyanines (ZnPcs) bearing one to eight positively-charged trimethylaminophenoxy groups are reported. All ZnPcs are highly soluble in polar organic solvents, and show fluorescence and singlet oxygen quantum yields in the ranges 0.11-0.21 and 0.16-0.47, respectively. The cytotoxicity of the ZnPcs depends on both the number of charges and their site of substitution (α vs. β) on the Pc isoindole units; the most promising for PDT application are the α-substituted di-cationic ZnPcs 6a and 17a.